Project Summary The breakneck pace of development towards potential uses of germline gene editing (GGE) in medicine raises some very crucial ethical questions. Though much research still needs to be done before GGE will be safe for use on humans, the technology has progressed very rapidly over the past few years. Among the most pressing of the ethical issues raised by GGE are those concerning human subjects research. Future clinical trials will confront novel ethical conundrums that are difficult to resolve given current guidelines. The most difficult of these conundrums are those concerning intergenerational monitoring ? long-term follow-up study not just of the original subjects, but also of their children and grandchildren. Numerous scientists, advisory panels, and professional associations have stated that such study will be necessary. There is currently little precedent in research ethics for the kind of intergenerational monitoring required here, and no precedent for the specific challenges posed by GGE. If future clinical trials are going to meet requirements of ethical research, the difficult issues raised by intergenerational monitoring must be resolved. This project will make an initial start on designing intergenerational monitoring protocols for future clinical trials of GGE. Drawing on prior work in clinical research ethics and the broader literature on the ethical, social, legal, and philosophical dimensions of GGE, the project will examine this unique set of ethical issues and apply these insights to the design of future clinical trials. The ultimate aim of the project will be to help advance research into the uses of GGE in medicine by dealing with a set of crucial barriers to future applications. In so doing, this project will contribute to the role of NHGRI and the ELSI program in providing leadership and guidance on the ethics of GGE in medicine, and on the potential use of this technology for the treatment of disease and improvement of human life.